Primary aim
For our primary analysis, multiple regression models were run to investigate the relationship between MS and brain volumes. The models were run separately (i.e. in parallel) for each brain region of interest (ROI) and the results are reported for ROIs that showed significant associations with MS. The models controlled for Sex, Age, Age Squared, Age by Sex interaction, and Intracranial Volume (ICV).
Model equation: \[\begin{align} ROI &= \beta_0 + \beta_1*Sex + \beta_2*Age + \beta_3*Age^2 + \beta_4*Sex*Age + \beta_5*ICV + \beta_6*MS + \epsilon \end{align}\]
Significant main effects: MS
With healthy controls as the reference group, the main effect in
milliliters (\(mL\)) of having MS,
after accounting for control variables, is shown in the
estimate column for each significant ROI in the table
below. Individual effects are described below the table.
#####
# Main effect Model: ROI ~ Sex + Age + Age^2 + Sex\*Age + MS + ICV
#####
run_model <- function(outcome){
#' run model for each ROI
f <- as.formula(sprintf("%s ~ Sex + Age + Age^2 + Sex*Age + MS + ICV", outcome))
res <- lm(f, data = df)
}
# run models searately
models <- ROI_INDICES %>%
purrr::map(run_model) %>%
purrr::map(tidy) %>%
setNames(ROI_INDICES) %>%
bind_rows(.id = 'ROI_INDEX') %>%
left_join(dict_df, by = c('ROI_INDEX')) %>% # join with ROI dictionary
select(ROI_INDEX, ROI_NAME, TISSUE_SEG, everything())
# use FDR correction
sig_main_effects_df <- models %>%
filter(term == 'MS1') %>%
mutate(p.value.adj = round(p.adjust(p.value, method='fdr'),4)) %>%
filter(p.value.adj < 0.05) %>%
mutate(p.value = round(p.value, 4)) %>%
arrange(by = TISSUE_SEG)
#Example interpretation: the right thalamus proper volume in the grey matter region of MS patients is 659 mL less on average compared to that of non-MS patients (95% CI: (xx,xx), p-value = 0.001)
sig_main_effects_df %>%
filter(term == 'MS1') %>%
select(-ROI_INDEX, -std.error, -statistic, -term)
# function to describe results
describe_main_effect <- function(row){
sprintf("The %s volume of MS patient is %.3f mL %s, on average, compared to that of controls (95%% CI: (%.3f, %.3f), p = %.3f).",
row$ROI_NAME,
round(abs(row$estimate), 2),
ifelse(sign(row$estimate) == 1, 'bigger', 'smaller'),
round(row$estimate - row$std.error, 3),
round(row$estimate + row$std.error, 3),
round(row$p.value, 3)
) |> invisible()
}
# split by rows
rows <- sig_main_effects_df %>%
split(seq_len(nrow(sig_main_effects_df)))
for (effect_row in rows){ # make list output
cat("\n")
cat("-", describe_main_effect(effect_row), "\n")
}
The Right Thalamus Proper volume of MS patient is 445.850 mL smaller, on average, compared to that of controls (95% CI: (-504.582, -387.127), p = 0.000).
The Left Thalamus Proper volume of MS patient is 445.840 mL smaller, on average, compared to that of controls (95% CI: (-506.099, -385.583), p = 0.000).
The Left Angular Gyrus volume of MS patient is 574.710 mL smaller, on average, compared to that of controls (95% CI: (-752.238, -397.182), p = 0.001).
The Left Calcarine Cortex volume of MS patient is 242.810 mL bigger, on average, compared to that of controls (95% CI: (165.218, 320.408), p = 0.002).
The Right Frontal Pole volume of MS patient is 178.830 mL smaller, on average, compared to that of controls (95% CI: (-232.753, -124.908), p = 0.001).
The Left Frontal Pole volume of MS patient is 213.700 mL smaller, on average, compared to that of controls (95% CI: (-276.337, -151.062), p = 0.001).
The Right Fusiform Gyrus volume of MS patient is 357.770 mL smaller, on average, compared to that of controls (95% CI: (-479.511, -236.028), p = 0.003).
The Right Inferior Occipital Gyrus volume of MS patient is 299.410 mL bigger, on average, compared to that of controls (95% CI: (193.993, 404.823), p = 0.005).
The Left Middle Cingulate Gyrus volume of MS patient is 306.440 mL smaller, on average, compared to that of controls (95% CI: (-386.836, -226.035), p = 0.000).
The Left Parietal Operculum volume of MS patient is 180.840 mL smaller, on average, compared to that of controls (95% CI: (-240.539, -121.149), p = 0.002).
The Right Precentral Gyrus volume of MS patient is 531.640 mL smaller, on average, compared to that of controls (95% CI: (-700.777, -362.494), p = 0.002).
The 3rd Ventricle volume of MS patient is 175.380 mL bigger, on average, compared to that of controls (95% CI: (148.588, 202.180), p = 0.000).
The Right Inferior Lateral Ventricle volume of MS patient is 68.610 mL bigger, on average, compared to that of controls (95% CI: (54.266, 82.960), p = 0.000).
The Left Inferior Lateral Ventricle volume of MS patient is 40.800 mL bigger, on average, compared to that of controls (95% CI: (29.030, 52.572), p = 0.000).
The Left Lateral Ventricle volume of MS patient is 1174.310 mL bigger, on average, compared to that of controls (95% CI: (778.903, 1569.717), p = 0.003).
The Frontal Lobe Wm Left volume of MS patient is 1979.050 mL bigger, on average, compared to that of controls (95% CI: (1377.032, 2581.071), p = 0.001).
The Corpus Callosum volume of MS patient is 457.840 mL smaller, on average, compared to that of controls (95% CI: (-622.614, -293.067), p = 0.005).